Cyclopropylmethyl Boronic Esters as General Reagents in Transition-Metal Catalyzed Homoallylation Reactions

TL;DR

This paper introduces a new method using boronic esters to create chiral compounds through metal-catalyzed reactions, useful for drug development and chemical synthesis.

Contribution

A novel approach using cyclopropylmethyl boronates for enantioenriched homoallylation via transmetalation in Negishi-type reactions.

Findings

The method enables the synthesis of arenes, ketones, and 1,5-dienes with chiral homoallylic scaffolds.

It allows late-stage functionalization of known drugs and preparation of biologically relevant compound precursors.

Mechanistic studies and DFT calculations support the transmetalation and ring-opening sequence.

Abstract

Herein we disclose
the use of cyclopropylmethyl boronates
as general
reagents in Negishi-type homoallylation reactions. This strategy provides
a novel approach to generate enantioenriched homoallyl-Zn species
through boron-to-zinc transmetalation. Subsequent sp2–sp3 cross-coupling offers a platform for the preparation of arenes,
ketones, and 1,5-dienes containing a chiral homoallylic scaffold.
The method has been applied to the late-stage functionalization of
known drugs and the preparation of precursors of biologically relevant
compounds. Mechanistic experiments and DFT calculations provide insight
into the transmetalation/ring-opening sequence.

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